Infectivity of Trypanosoma cruzi strains is associated with differential expression of surface glycoproteins with differential Ca2+ signalling activity.
Mammalian cell invasion assays, using metacyclic trypomastigotes of Trypanosoma cruzi G and CL strains, showed that the CL strain enters target cells in several-fold higher numbers as compared with the G strain. Analysis of expression of surface glycoproteins in metacyclic forms of the two strains by iodination, immunoprecipitation and FACS, revealed that gp90, undetectable in the CL strain, is one of the major surface molecules in the G strain, that expression of gp82 is comparable in both strains and that gp35/50 is expressed at lower levels in the CL strain. Purified gp90 and gp35/50 bound more efficiently than gp82 to cultured HeLa cells. However, the intensity of the Ca2+ response triggered in HeLa cells by gp82 was significantly higher than that induced by gp35/50 or gp90. Most of the Ca2+ signalling activity of the metacyclic extract towards HeLa cells was due to gp82 and was inhibitable by gp82-specific monoclonal antibody 3F6. Ca2+ mobilization was also triggered in metacyclic trypomastigotes by host-cell components; it was mainly gp82-mediated and more intense in the CL than in the G strain. We propose that expression of gp90 and gp35/50 at high levels impairs binding of metacyclic forms to host cells through productive gp82-mediated interaction, which leads to the target-cell and parasite Ca2+ mobilization required for invasion. Analysis of metacyclic forms of eight additional T. cruzi strains corroborated the inverse correlation between infectivity and expression of gp90 and gp35/50.
Ruiz
R C
RC
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Botucatu, 862-6 andar, 04023-062, S-ao Paulo, S.P., Brazil.
Favoreto
S
S
Dorta
M L
ML
Oshiro
M E
ME
Ferreira
A T
AT
Manque
P M
PM
Yoshida
N
N
D000818:Animals; D000913:Antibodies, Protozoan / Q000502:physiology; D000953:Antigens, Protozoan / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D008970:Molecular Weight; D015800:Protozoan Proteins / Q000737:chemistry / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000472:pathogenicity*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000502:physiology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; C044186:glycoprotein GP90, Trypanosoma cruzi; D002118:Calcium